Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes
Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
23 February 2019
|
| In: |
Neurobiology of disease
Year: 2019, Jahrgang: 127, Pages: 76-86 |
| ISSN: | 1095-953X |
| DOI: | 10.1016/j.nbd.2019.02.019 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1016/j.nbd.2019.02.019 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S096999611930049X 
|
| Verfasserangaben: | Ryan B. Griggs, Diogo F. Santos, Don E. Laird, Suzanne Doolen, Renee R. Donahue, Caitlin R. Wessel, Weisi Fu, Ghanshyam P. Sinha, Pingyuan Wang, Jia Zhou, Sebastian Brings, Thomas Fleming, Peter P. Nawroth, Keiichiro Susuki, Bradley K. Taylor |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1671738438 | ||
| 003 | DE-627 | ||
| 005 | 20220816212511.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190821s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.nbd.2019.02.019 |2 doi | |
| 035 | |a (DE-627)1671738438 | ||
| 035 | |a (DE-599)KXP1671738438 | ||
| 035 | |a (OCoLC)1341238052 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Griggs, Ryan |e VerfasserIn |0 (DE-588)1193130808 |0 (DE-627)1671739043 |4 aut | |
| 245 | 1 | 0 | |a Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes |c Ryan B. Griggs, Diogo F. Santos, Don E. Laird, Suzanne Doolen, Renee R. Donahue, Caitlin R. Wessel, Weisi Fu, Ghanshyam P. Sinha, Pingyuan Wang, Jia Zhou, Sebastian Brings, Thomas Fleming, Peter P. Nawroth, Keiichiro Susuki, Bradley K. Taylor |
| 264 | 1 | |c 23 February 2019 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 21.08.2019 | ||
| 520 | |a Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related spinal mechanisms of PDN in type 2 diabetes using db/db mice, an established model of type 2 diabetes, and intrathecal injection of MG in conventional C57BL/6J mice. Administration of either a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the catabolic enzyme for MG, attenuated heat hypersensitivity in db/db mice. In C57BL/6J mice, intrathecal administration of MG produced signs of both evoked (heat and mechanical hypersensitivity) and affective (conditioned place avoidance) pain. MG-induced Ca2+ mobilization in lamina II dorsal horn neurons of C57BL/6J mice was exacerbated in db/db, suggestive of MG-evoked central sensitization. Pharmacological and/or genetic inhibition of transient receptor potential ankyrin subtype 1 (TRPA1), adenylyl cyclase type 1 (AC1), protein kinase A (PKA), or exchange protein directly activated by cyclic adenosine monophosphate (Epac) blocked MG-evoked hypersensitivity in C57BL/6J mice. Similarly, intrathecal administration of GERP10, or inhibitors of TRPA1 (HC030031), AC1 (NB001), or Epac (HJC-0197) attenuated hypersensitivity in db/db mice. We conclude that MG and sensitization of a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice. Our results warrant clinical investigation of MG scavengers, glyoxalase inducers, and spinally-directed pharmacological inhibitors of a MG-TRPA1-AC1-Epac pathway for the treatment of PDN in type 2 diabetes. | ||
| 650 | 4 | |a AC1 | |
| 650 | 4 | |a Epac | |
| 650 | 4 | |a Glyoxalase | |
| 650 | 4 | |a Methylglyoxal | |
| 650 | 4 | |a Neuropathic pain | |
| 650 | 4 | |a Painful diabetic neuropathy | |
| 650 | 4 | |a PKA | |
| 650 | 4 | |a Spinal | |
| 650 | 4 | |a TRPA1 | |
| 650 | 4 | |a Type 2 diabetes | |
| 700 | 1 | |a Santos, Diogo F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Laird, Don E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Doolen, Suzanne |e VerfasserIn |4 aut | |
| 700 | 1 | |a Donahue, Renee R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wessel, Caitlin R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fu, Weisi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sinha, Ghanshyam P. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wang, Pingyuan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhou, Jia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brings, Sebastian |e VerfasserIn |0 (DE-588)1155036212 |0 (DE-627)1016344155 |0 (DE-576)501404430 |4 aut | |
| 700 | 1 | |a Fleming, Thomas |d 1982- |e VerfasserIn |0 (DE-588)1034445294 |0 (DE-627)745607365 |0 (DE-576)382066804 |4 aut | |
| 700 | 1 | |a Nawroth, Peter Paul |d 1954- |e VerfasserIn |0 (DE-588)1020504897 |0 (DE-627)69123941X |0 (DE-576)360517692 |4 aut | |
| 700 | 1 | |a Susuki, Keiichiro |e VerfasserIn |4 aut | |
| 700 | 1 | |a Taylor, Bradley K. |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neurobiology of disease |d [Amsterdam] : Elsevier, 1994 |g 127(2019), Seite 76-86 |h Online-Ressource |w (DE-627)268125414 |w (DE-600)1471408-5 |w (DE-576)27234947X |x 1095-953X |7 nnas |a Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes |
| 773 | 1 | 8 | |g volume:127 |g year:2019 |g pages:76-86 |g extent:11 |a Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.nbd.2019.02.019 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S096999611930049X |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190821 | ||
| 993 | |a Article | ||
| 994 | |a 2019 | ||
| 998 | |g 1020504897 |a Nawroth, Peter Paul |m 1020504897:Nawroth, Peter Paul |d 910000 |d 910100 |e 910000PN1020504897 |e 910100PN1020504897 |k 0/910000/ |k 1/910000/910100/ |p 13 | ||
| 998 | |g 1034445294 |a Fleming, Thomas |m 1034445294:Fleming, Thomas |d 910000 |d 910100 |e 910000PF1034445294 |e 910100PF1034445294 |k 0/910000/ |k 1/910000/910100/ |p 12 | ||
| 998 | |g 1155036212 |a Brings, Sebastian |m 1155036212:Brings, Sebastian |d 910000 |d 910100 |e 910000PB1155036212 |e 910100PB1155036212 |k 0/910000/ |k 1/910000/910100/ |p 11 | ||
| 999 | |a KXP-PPN1671738438 |e 3507835010 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title_sort":"Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes","title":"Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes"}],"name":{"displayForm":["Ryan B. Griggs, Diogo F. Santos, Don E. Laird, Suzanne Doolen, Renee R. Donahue, Caitlin R. Wessel, Weisi Fu, Ghanshyam P. Sinha, Pingyuan Wang, Jia Zhou, Sebastian Brings, Thomas Fleming, Peter P. Nawroth, Keiichiro Susuki, Bradley K. Taylor"]},"origin":[{"dateIssuedKey":"2019","dateIssuedDisp":"23 February 2019"}],"id":{"doi":["10.1016/j.nbd.2019.02.019"],"eki":["1671738438"]},"physDesc":[{"extent":"11 S."}],"relHost":[{"title":[{"title_sort":"Neurobiology of disease","title":"Neurobiology of disease"}],"language":["eng"],"disp":"Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetesNeurobiology of disease","origin":[{"dateIssuedDisp":"1994-","publisher":"Elsevier ; Academic Press","publisherPlace":"[Amsterdam] ; Orlando, Fla.","dateIssuedKey":"1994"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"eki":["268125414"],"zdb":["1471408-5"],"issn":["1095-953X"]},"titleAlt":[{"title":"Experimental neurology / B"}],"note":["Gesehen am 18.10.2022"],"recId":"268125414","part":{"volume":"127","pages":"76-86","year":"2019","extent":"11","text":"127(2019), Seite 76-86"},"type":{"media":"Online-Ressource","bibl":"periodical"},"pubHistory":["1.1994 -"]}],"person":[{"roleDisplay":"VerfasserIn","role":"aut","given":"Ryan","display":"Griggs, Ryan","family":"Griggs"},{"given":"Diogo F.","roleDisplay":"VerfasserIn","role":"aut","display":"Santos, Diogo F.","family":"Santos"},{"display":"Laird, Don E.","role":"aut","roleDisplay":"VerfasserIn","given":"Don E.","family":"Laird"},{"family":"Doolen","display":"Doolen, Suzanne","role":"aut","roleDisplay":"VerfasserIn","given":"Suzanne"},{"family":"Donahue","role":"aut","roleDisplay":"VerfasserIn","given":"Renee R.","display":"Donahue, Renee R."},{"family":"Wessel","roleDisplay":"VerfasserIn","role":"aut","given":"Caitlin R.","display":"Wessel, Caitlin R."},{"family":"Fu","display":"Fu, Weisi","given":"Weisi","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Sinha","display":"Sinha, Ghanshyam P.","given":"Ghanshyam P.","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Wang","display":"Wang, Pingyuan","role":"aut","roleDisplay":"VerfasserIn","given":"Pingyuan"},{"family":"Zhou","display":"Zhou, Jia","role":"aut","roleDisplay":"VerfasserIn","given":"Jia"},{"display":"Brings, Sebastian","roleDisplay":"VerfasserIn","role":"aut","given":"Sebastian","family":"Brings"},{"roleDisplay":"VerfasserIn","role":"aut","given":"Thomas","display":"Fleming, Thomas","family":"Fleming"},{"family":"Nawroth","given":"Peter Paul","roleDisplay":"VerfasserIn","role":"aut","display":"Nawroth, Peter Paul"},{"family":"Susuki","roleDisplay":"VerfasserIn","role":"aut","given":"Keiichiro","display":"Susuki, Keiichiro"},{"family":"Taylor","display":"Taylor, Bradley K.","given":"Bradley K.","roleDisplay":"VerfasserIn","role":"aut"}],"language":["eng"],"note":["Gesehen am 21.08.2019"],"recId":"1671738438","type":{"media":"Online-Ressource","bibl":"article-journal"}} | ||
| SRT | |a GRIGGSRYANMETHYLGLYO2320 | ||